The signal in the noise: size and dynamics of topological domains from DNA fluctuations

In the cell, long DNA molecules carry genetic information and must be stored while remaining accessible to interact with various biomolecules that control the reading and processing of this information. DNA-binding proteins often intervene in these processes by bringing together two distant DNA sites, thus inducing transient topological domains. 

The work presented in this seminar shows how taking into account fluctuations in DNA extension, in addition to average extension, provides additional information on protein-DNA interactions that is otherwise undetectable.

The NUMEV Seminars are open to a wide audience of students and researchers from all disciplines, who wish to find out more about the current research areas of the NUMEV-MIPS (Mathematics, Informatics, Physics and Systems) community, or about opportunities to develop their skills and know-how.

"The signal in the noise: size and dynamics of topological domains from DNA fluctuations".

Enrico Carlon, Soft Matter and Biophysics, KU Leuven, Belgium

Abstract

In the cell, long DNA molecules carry the genetic information and must be stored yet remain accessible to interact with various biomolecules which control for read out and processing. DNA-binding proteins often mediate these processes by bringing two distant DNA sites together, thereby inducing (transient) topological domains. In order to understand the dynamics and molecular architecture of protein-induced topological domains in DNA, quantitative and time-resolved approaches are required.

Here we present a methodology to determine the size and dynamics of topological domains using the analysis of fluctuations: a protein-binding event causes a drop in the variance in the end-end distance of a stretched over-wound DNA molecule. Using a combination of high-speed magnetic tweezers experiments, Monte Carlo simulations, and analytical theory, we map out the dependence of DNA extension fluctuations as a function of supercoiling density and external force. We demonstrate how transient (partial) dissociation of DNA bridging proteins results in dynamic sampling of different topological states.

Our work highlights how considering DNA extension fluctuations, in addition to the mean extension, provides additional information and enables the investigation of protein-DNA interactions that are otherwise not detectable.